146950-67-6Relevant articles and documents
(1H-Imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: A novel class of potent MSK-1-inhibitors
Bamford, Mark J.,Alberti, Michael J.,Bailey, Nicholas,Davies, Susannah,Dean, David K.,Gaiba, Alessandra,Garland, Stephen,Harling, John D.,Jung, David K.,Panchal, Terence A.,Parr, Christopher A.,Steadman, Jon G.,Takle, Andrew K.,Townsend, James T.,Wilson, David M.,Witherington, Jason
, p. 3402 - 3406 (2005)
A novel series of imidazo[4,5-c]pyridines bearing a 1,2,5-oxadiazol-3- ylamine functionality has been developed. These are potent inhibitors of mitogen and stress-activated protein kinase-1.
HETEROCYCLYC SULFONAMIDES HAVING EDG-I ANTAGONISTIC ACTIVITY
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Page/Page column 170, (2008/12/05)
The invention relates to chemical compounds of formula (I), (Ia) and (Ib) or pharmaceutically acceptable salts thereof, which possess Edg-1 antagonistic activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an anti-cancer effect in a warm-blooded animal, such as man.
Discovery of aminofurazan-azabenzimidazoles as inhibitors of rho-kinase with high kinase selectivity and antihypertensive activity
Stavenger, Robert A.,Cui, Haifeng,Dowdell, Sarah E.,Franz, Robert G.,Gaitanopoulos, Dimitri E.,Goodman, Krista B.,Hilfiker, Mark A.,Ivy, Robert L.,Leber, Jack D.,Marino Jr., Joseph P.,Oh, Hye-Ja,Viet, Andrew Q.,Xu, Weiwei,Ye, Guosen,Zhang, Daohua,Zhao, Yongdong,Jolivette, Larry J.,Head, Martha S.,Semus, Simon F.,Elkins, Patricia A.,Kirkpatrick, Robert B.,Dul, Edward,Khandekar, Sanjay S.,Yi, Tracey,Jung, David K.,Wright, Lois L.,Smith, Gary K.,Behm, David J.,Doe, Christopher P.,Bentley, Ross,Chen, Zunxuan X.,Hu, Erding,Lee, Dennis
, p. 2 - 5 (2007/10/03)
The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension. Despite many available treatments, hypertension remains a prevalent problem. In fact, some 30% of hypertensive patients are unable to reach their blood pressure goals. Thus, a new anti-hypertensive treatment, which acts on a broader patient population, would be an important addition to existing treatments. A number of vasoconstrictive agents, including angiotensin II, endothelin-1, and urotensin-II, exert their effect through RhoA and the downstream kinase Rho-kinase (ROCK1).1 Because of its central role in the control of smooth muscle contraction, inhibition of ROCK1 could lead to a more broadly efficacious anti-hypertensive agent.2 ROCK1 inhibitors have been shown to relax vascular smooth muscle and lower blood pressure in several animal models of hypertension.3 Therefore, we began an effort to identify potent ROCK1 inhibitors with pharmacokinetic profiles consistent with once daily oral dosing.